Validating Biomarkers for the Prodrome and Transition to Psychosis in Shanghai 7. Project Summary/Abstract: The identification of people at risk of developing psychosis is central to the development of early intervention and prevention strategies for schizophrenia. There is a worldwide movement in the study of populations at the putatively prodromal, clinical high-risk (CHR) stage led mainly by researchers in Australia, Europe, and North America (North American Prodrome Longitudinal Studies/NAPLS). Within the Asian Network for Early Psychosis, Taiwan and Singapore have started to address the putatively prodromal population. To our knowledge, we are the only group carrying out a CHR study, an R21 in collaboration with the Shanghai Mental Health Center (SMHC), MH093294 (Fogarty/NIH, Broadening the Investigation of Psychosis Prodrome to Different Cultural Groups). The preliminary study, which has already begun, contains four major components: a) clinical assessment of prodromal subjects using the Structured Interview for Prodromal Syndromes and Scale of Prodromal Symptoms (SIPS/SOPS) (translated into Chinese by the PI of the R21, Dr. Li); b) neurocognitive assessment with the MATRICS battery, c) stigma, and d) event related potentials. In addition, blood samples will be collected and stored for future genetic analyses. Our current proposal, in response to the RFA-AI-12-021: U.S.-China Program for Biomedical Collaborative Research (R01) will build upon and extend the R21 at the SMHC by expanding the sample substantially and bring in structural, DTI and resting state measures of magnetic resonance imaging (MRI). We will work collaboratively with researchers at the SMHC to design and initiate a sustainable CHR to psychosis longitudinal program of research in China. The SMHC, a World Health Organization designated research center for mental health, has excellent clinical and biomedical research technical resources that can carry out a first-rate study in collaboration with the US team. Our specific aims are to: 1. Identify clinical and biomarker abnormalities in CHR vs. Controls; 2. Replicate prediction of psychosis algorithms from the NAPLS study and; 3. Demonstrate increasing brain abnormalities with conversion to psychosis. Two hundred CHR and 100 controls, age 15-45, will be assessed at baseline and followed for one year, resulting in an estimated 40 converters to psychosis. With an estimated retention rate of 75%, 30 CHR who become psychotic, 120 who do not become psychotic and 75 controls will be assessed at conversion or 1 year follow-up with an extensive battery of clinical and biological measures.